Search

Introduction: The Multidomain Alzheimer Preventive Trial (MAPT) assessed the efficacy of omega-3 fatty acid supplementation, a multidomain intervention (MI), or a combination of both on cognition. Impact according to cerebral amyloid status was evaluated by PET scan., Methods: Participants were nondemented and had memory complaints, limitation in one instrumental activity of daily living, or slow gait. The primary outcome was a change from baseline in 36 months measured with a cognitive composite Z score., Results: No effect was observed on cognition in the negative amyloid group (n = 167). In the positive amyloid group (n = 102), we observed a difference of 0.708 and 0.471 in the cognitive composite score between the MI plus omega-3 fatty acid group, the MI alone group, and the placebo group, respectively., Discussion: MI alone or in combination with omega-3 fatty acids was associated with improved primary cognitive outcome in subjects with positive amyloid status., Trial Registration: ClinicalTrials.gov Identifier: NCT01513252., (Copyright © 2019 the Alzheimer's Association. All rights reserved.)

Background: In MAPT (Multidomain Alzheimer Preventive Trial), a cognitive effect of multidomain intervention (MI) was showed in non-demented subjects with positive amyloid PET. However, screening eligible patients for multidomain intervention by PET is difficult to generalize in real-world settings. Methods: MAPT study was a 3-year, randomized, placebo-controlled trial followed by a 2-year observational and optional extension. All participants were non-demented and randomly assigned (1:1:1:1) to the MI plus omega 3, MI plus placebo, omega 3 alone, or placebo alone group. The objectives were to assess the cognitive effect of MAPT interventions (omega 3 supplementation, MI, combined intervention) in non-demented subjects according to amyloid blood status at 12, 36, and 60 months. In this subgroup analysis (n = 483), amyloid status was defined by plasma Aβ42/40 ratio (cutoff ≤ 0.0107). The primary outcome measure was the change in cognitive composite score after a 1, 3, and 5-year clinical follow-up. Results: The intention-to-treat (ITT) population included 483 subjects (161 positive and 322 negative amyloid participants based on plasma Aβ42/40 ratio). In the positive amyloid ITT population, we showed a positive effect of MI plus omega 3 on the change in composite cognitive score in 12 (raw p =.0350, 0.01917, 95% CI = [0.0136 to 0.3699]) and 36 months (raw p =.0357, 0.2818, 95% CI = [0.0190 to 0.5446]). After correction of multiple comparisons and adjustments, these differences were not significant (adjusted p =.1144 and.0690). In the per-protocol positive amyloid group (n = 154), we observed a significant difference between the combined intervention and placebo groups at 12 (p =.0313, 0.2424, 0.0571 to 0.4276) and 36 months (p =.0195, 0.3747, 0.1055 to 0.6439) persisting after adjustment. In the ITT and per-protocol analyses, no cognitive effect was observed in the positive and negative amyloid group at 60-month visit. Conclusions: These findings suggest a benefit of MI plus omega 3 in positive blood amyloid subjects. This promising trend needs to be confirmed before using blood biomarkers for screening in preventive trials. Trial registration: ClinicalTrials.gov Identifier: NCT01513252. [ABSTRACT FROM AUTHOR]

Background: Recruitment is often a bottleneck in secondary prevention trials in Alzheimer disease (AD). Furthermore, screen-failure rates in these trials are typically high due to relatively low prevalence of AD pathology in individuals without dementia, especially among cognitively unimpaired. Prescreening on AD risk factors may facilitate recruitment, but the efficiency will depend on how these factors link to participation rates and AD pathology. We investigated whether common AD-related factors predict trial-ready cohort participation and amyloid status across different prescreen settings. Methods: We monitored the prescreening in four cohorts linked to the European Prevention of Alzheimer Dementia (EPAD) Registry (n = 16,877; mean ± SD age = 64 ± 8 years). These included a clinical cohort, a research in-person cohort, a research online cohort, and a population-based cohort. Individuals were asked to participate in the EPAD longitudinal cohort study (EPAD-LCS), which serves as a trial-ready cohort for secondary prevention trials. Amyloid positivity was measured in cerebrospinal fluid as part of the EPAD-LCS assessment. We calculated participation rates and numbers needed to prescreen (NNPS) per participant that was amyloid-positive. We tested if age, sex, education level, APOE status, family history for dementia, memory complaints or memory scores, previously collected in these cohorts, could predict participation and amyloid status. Results: A total of 2595 participants were contacted for participation in the EPAD-LCS. Participation rates varied by setting between 3 and 59%. The NNPS were 6.9 (clinical cohort), 7.5 (research in-person cohort), 8.4 (research online cohort), and 88.5 (population-based cohort). Participation in the EPAD-LCS (n = 413 (16%)) was associated with lower age (odds ratio (OR) age = 0.97 [0.95–0.99]), high education (OR = 1.64 [1.23–2.17]), male sex (OR = 1.56 [1.19–2.04]), and positive family history of dementia (OR = 1.66 [1.19–2.31]). Among participants in the EPAD-LCS, amyloid positivity (33%) was associated with higher age (OR = 1.06 [1.02–1.10]) and APOE ɛ4 allele carriership (OR = 2.99 [1.81–4.94]). These results were similar across prescreen settings. Conclusions: Numbers needed to prescreen varied greatly between settings. Understanding how common AD risk factors link to study participation and amyloid positivity is informative for recruitment strategy of studies on secondary prevention of AD. [ABSTRACT FROM AUTHOR]

Introduction: The Multidomain Alzheimer Preventive Trial (MAPT) assessed the efficacy of omega‐3 fatty acid supplementation, a multidomain intervention (MI), or a combination of both on cognition. Impact according to cerebral amyloid status was evaluated by PET scan. Methods: Participants were nondemented and had memory complaints, limitation in one instrumental activity of daily living, or slow gait. The primary outcome was a change from baseline in 36 months measured with a cognitive composite Z score. Results: No effect was observed on cognition in the negative amyloid group (n = 167). In the positive amyloid group (n = 102), we observed a difference of 0.708 and 0.471 in the cognitive composite score between the MI plus omega‐3 fatty acid group, the MI alone group, and the placebo group, respectively. Discussion: MI alone or in combination with omega‐3 fatty acids was associated with improved primary cognitive outcome in subjects with positive amyloid status. Trial Registration: ClinicalTrials.gov Identifier: NCT01513252. [ABSTRACT FROM AUTHOR]

Objective: To determine whether brain amyloid burden in elderly patients with narcolepsy type 1 (NT1) is lower than in controls, and to assess in patients with NT1 the relationships between amyloid burden, cerebral spinal fluid (CSF) markers of Alzheimer disease (AD), CSF orexin-A, and cognitive profile.Methods: Cognitive and 18 F-florbetapir positron emission tomography (PET) data were compared in patients with NT1 aged ≥ 65 years (n = 23) and in age- and sex-matched controls free of clinical dementia selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI; n = 69) and the Multi-Domain Intervention Alzheimer's Prevention Trial (MAPT-18F AV45-PET; n = 23) cohorts. The standardized uptake values (SUVs) of the cortical retention index for 6 regions of interest were computed and averaged to create a mean SUV ratio normalized to 3 subcortical reference regions (cerebellum, pons, and a composite region). A cortical/cerebellum SUV ratio ≥ 1.17 defined positive PET amyloid.Results: Lower cortical amyloid burden was observed in the NT1 than in the ADNI and MAPT-AV45 groups (mean cortical/cerebellum SUV ratios = 0.95 ± 0.15, 1.11 ± 0.18 [p < 0.0001], and 1.14 ± 0.17 [p = 0.0005], respectively). Similar results were obtained with all subcortical reference regions and for all cortical regions of interest, except cingulum. Only 1 patient with NT1 (4.4%) had positive PET amyloid compared with 27.5% in the ADNI and 30.4% in the MAPT-AV45 group. In the NT1 group, cortical or regional amyloid load was not associated with CSF orexin-A, CSF AD biomarkers, or neuropsychological profile.Interpretation: Lower brain amyloid burden, assessed by 18 F-florbetapir PET, in patients with NT1 suggests delayed appearance of amyloid plaques. ANN NEUROL 2019;85:74-83. [ABSTRACT FROM AUTHOR]